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1.
Gamma globulin combined with acyclovir for children with infectious mononucleosis and their effect on immune function
Li, Y., Chen, B.
American journal of translational research. 2023;15(6):4399-4407
Abstract
BACKGROUND Infectious mononucleosis (IM) is characterized by pharyngitis, cervical lymphadenopathy, fatigue and fever. IM is most commonly seen in primary Epstein-Barr virus (EBV) infection, with higher occurrence in children. OBJECTIVE To explore the value of gamma globulin combined with acyclovir for IM children and their impact on immune function. METHODS This prospective randomized controlled study recruited 111 children under 14 years old with IM from Anhui Provincial Children's Hospital during March 2019 and March 2022. Among them, 11 children dropped out, and 100 eligible children were randomized 1:1 into a control group and a study group. The control group received acyclovir, and the study group received additional gamma globulin. The baseline data, clinical efficacy, immune function, and adverse reactions were collected and compared. RESULTS The study group had a shorter antipyretic time, lymph node reduction time, pharyngitis improvement time, and hospital stay compared to the control group (P < 0.05). The study group yielded lower levels of total white blood cell count, alanine aminotransferase, and creatine kinase-MB than the control group (P < 0.05). After treatment, the levels of CD3+ and CD8+ were lower, and the levels of CD4+, CD4+/CD8+, IgA, and IgG were higher in the study group than those in the control group (all P < 0.05). The incidence of adverse reactions between the two groups was comparable (14.00% vs. 24.00%). The positive rates of EBV-specific antibody and nuclear antigen in the study group were lower than those in the control group (P < 0.05). CONCLUSION The combined treatment of gamma globulin and acyclovir is a promising alternative for patients with IM compared to acyclovir alone. This combined regimen shortens the duration of clinical manifestations in children, promotes the recovery of laboratory indices, improves clinical efficacy, and enhances immune function. Furthermore, its safety profile is acceptable, warranting its further promotion.
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2.
Randomized Trial of Hyperimmune Globulin for Congenital CMV Infection - 2-Year Outcomes
Hughes, B. L., Clifton, R. G., Rouse, D. J., Saade, G. R., Dinsmoor, M. J., Reddy, U. M., Pass, R., Allard, D., Mallett, G., MacPherson, C., et al
The New England journal of medicine. 2023;389(19):1822-1824
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Editor's Choice
PICO Summary
Population
Pregnant women with primary maternal cytomegalovirus (CMV) infection (n= 399).
Intervention
Monthly infusions of CMV hyperimmune globulin until delivery (n= 206).
Comparison
Placebo (n= 193).
Outcome
This planned 2-year follow-up study involved the children of the enrolled women to evaluate whether CMV hyperimmune globulin improves childhood outcomes. Partial data on 2-year outcomes were available for 360 children (90%). Death or CMV infection with severe disability occurred in 20 of the 149 children (13.4%) in the hyperimmune globulin group and in 15 of the 149 children (10.1%) in the placebo group (relative risk, 1.33; 95% confidence interval [0.71, 2.50]. No material differences were found between the groups in the incidence of any component of the composite outcome or in any other outcome at 24 months, including severe disability with or without congenital CMV infection. No deaths occurred after the delivery hospitalization.
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Role of Preemptive Cytomegalovirus Hyperimmunoglobulin in Cytomegalovirus Viremia Following Stem Cell Transplant: An Integrative Review
Whittaker, J., Martinez, A., Dains, J. E.
Journal of the advanced practitioner in oncology. 2023;14(7):620-630
Abstract
INTRODUCTION Cytomegalovirus (CMV) is a major cause of morbidity and mortality in stem cell transplant (SCT) patients. Cytomegalovirus hyperimmunoglobulin (CMV-HIG) therapy has been described in the solid organ transplant setting. However, no review has focused on preemptive use of intravenous CMV immunoglobulins in the SCT setting. This review aims to consolidate findings regarding the preemptive use of CMV-HIG for CMV viremia in SCT patients. METHODS PubMed and Scopus were searched using specific search criteria for publications from 2011 to 2021. Search terms were: cytomegalovirus, CMV, immunoglobulins, immunoglobulin, IVIG, CMVIG, hematopoietic stem cell transplantation, and stem cell. Included studies discussed stem cell transplantation, immunoglobulins, and cytomegalovirus. 366 articles were identified from the search. Five articles met the inclusion and exclusion criteria. RESULTS Preemptive CMV-HIG resulted in an overall response in 65% to 100% of patients with a clearance time of 14 to 21 days. Early use of CMV-HIG may shorten clearance time. No treatment-related mortality or serious adverse events were associated. CONCLUSION CMV-HIG is an effective treatment option in SCT patients that is as safe as antivirals alone. Preemptive CMV-HIG with antivirals may provide the added advantage of reduced time to viremia clearance without adding renal injury. Larger, prospective studies are needed to evaluate CMV-HIG's impact on time to viremia clearance and the effectiveness of preemptive CMV-HIG use with antivirals.
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4.
Effect of oseltamivir phosphate versus placebo on platelet recovery and plasma leakage in adults with dengue and thrombocytopenia; a phase 2, multicenter, double-blind, randomized trial
Tunjungputri RN, Riswari SF, Pramudo SG, Kuntjoro L, Alisjahbana B, Nugraha HG, van der Ven A, Gasem MH, de Mast Q
PLoS Neglected Tropical Diseases. 2022;16(1):e0010051
Abstract
BACKGROUND Thrombocytopenia, bleeding and plasma leakage are major complications of dengue. Activation of endogenous sialidases with desialylation of platelets and endothelial cells may underlie these complications. We aimed to assess the effects of the neuraminidase inhibitor oseltamivir on platelet recovery and plasma leakage in dengue. METHODS We performed a phase 2, double-blind, multicenter, randomized trial in adult dengue patients with thrombocytopenia (<70,000/μl) and a duration of illness ≤ 6 days. Oseltamivir phosphate 75mg BID or placebo were given for a maximum of five days. Primary outcomes were the time to platelet recovery (≥ 100,000/μl) or discharge from hospital and the course of measures of plasma leakage. RESULTS A total of 70 patients were enrolled; the primary outcome could be assessed in 64 patients (31 oseltamivir; 33 placebo). Time to platelet count ≥100,000/μl (n = 55) or discharge (n = 9) were similar in the oseltamivir and placebo group (3.0 days [95% confidence interval, 2.7 to 3.3] vs. 2.9 days [2.5 to 3.3], P = 0.055). The kinetics of platelet count and parameters of plasma leakage (gall bladder thickness, hematocrit, plasma albumin, syndecan-1) were also similar between the groups. DISCUSSION In this trial, adjunctive therapy with oseltamivir phosphate had no effect on platelet recovery or plasma leakage parameters. TRIAL REGISTRATION ISRCTN35227717.
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The number of cases, mortality and treatments of viral hemorrhagic fevers: A systematic review
Belhadi D, El Baied M, Mulier G, Malvy D, Mentré F, Laouénan C
PLoS neglected tropical diseases. 2022;16(10):e0010889
Abstract
BACKGROUND Viral hemorrhagic fevers (VHFs) are a group of diseases, which can be endemo-epidemic in some areas of the world. Most of them are characterized by outbreaks, which, occur irregularly and are hard to predict. Innovative medical countermeasures are to be evaluated but due to the field specificities of emerging VHF, challenges arise when implementing clinical studies. To assess the state of the art around VHFs, we conducted a systematic review for all reports and clinical studies that included specific results on number of cases, mortality and treatment of VHFs. METHODS The search was conducted in January 2020 based on PRISMA guidelines (PROSPERO CRD42020167306). We searched reports on the WHO and CDC websites, and publications in three international databases (MEDLINE, Embase and CENTRAL). Following the study selection process, qualitative and quantitative data were extracted from each included study. A narrative synthesis approach by each VHF was used. Descriptive statistics were conducted including world maps of cases number and case fatality rates (CFR); summary tables by VHF, country, time period and treatment studies. RESULTS We identified 141 WHO/CDC reports and 126 articles meeting the inclusion criteria. Most of the studies were published after 2010 (n = 97 for WHO/CDC reports and n = 93 for publications) and reported number of cases and/or CFRs (n = 141 WHO/CDC reports and n = 88 publications). Results varied greatly depending on the outbreak or cluster and across countries within each VHF. A total of 90 studies focused on Ebola virus disease (EVD). EVD outbreaks were reported in Africa, where Sierra Leone (14,124 cases; CFR = 28%) and Liberia (10,678 cases; CFR = 45%) reported the highest cases numbers, mainly due to the 2014-2016 western Africa outbreak. Crimean-Congo hemorrhagic fever (CCHF) outbreaks were reported from 31 studies in Africa, Asia and Europe, where Turkey reported the highest cases number (6,538 cases; CFR = 5%) and Afghanistan the last outbreak in 2016/18 (293 cases; CFR = 43%). Regarding the 38 studies reporting results on treatments, most of them were non-randomized studies (mainly retrospective or non-randomized comparative studies), and only 10 studies were randomized controlled trials. For several VHFs, no specific investigational therapeutic option with strong proof of effectiveness on mortality was identified. CONCLUSION We observed that number of cases and CFR varied greatly across VHFs as well as across countries within each VHF. The number of studies on VHF treatments was very limited with very few randomized trials and no strong proof of effectiveness of treatment against most of the VHFs. Therefore, there is a high need of methodologically strong clinical trials conducted in the context of VHF.
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Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial
Malavige GN, Jeewandara C, Wijewickrama A, Gunasinghe D, Mahapatuna SD, Gangani C, Vimalachandran V, Jayaratne G, Perera Y, Wanigatunga C, et al
PLoS neglected tropical diseases. 2022;16(6):e0010123
Abstract
BACKGROUND Rupatadine was previously shown to reduce endothelial dysfunction in vitro, reduced vascular leak in dengue mouse models and to reduce the extent of pleural effusions and thrombocytopenia in patients with acute dengue. Therefore, we sought to determine the efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever (DHF) in patients with acute dengue. METHODS AND FINDINGS A phase 2, randomised, double blind, placebo controlled clinical trial was carried out in patients with acute dengue in Sri Lanka in an outpatient setting. Patients with ≤3 days since the onset of illness were either recruited to the treatment arm of oral rupatadine 40mg for 5 days (n = 123) or the placebo arm (n = 126). Clinical and laboratory features were measured daily to assess development of DHF and other complications. 12 (9.7%) patients developed DHF in the treatment arm compared to 22 (17.5%) who were on the placebo although this was not significant (p = 0.09, relative risk 0.68, 95% CI 0.41 to 1.08). Rupatadine also significantly reduced (p = 0.01) the proportion of patients with platelet counts <50,000 cells/mm3 and significantly reduced (p = 0.04) persisting vomiting, headache and hepatic tenderness (p<0.0001) in patients. However, there was no difference in the duration of illness and in the proportion of individuals who required hospital admission in both treatment arms. Only 2 patients on rupatadine and 3 patients on the placebo developed shock, while bleeding manifestations were seen in 6 patients on rupatadine and 7 patients on the placebo. CONCLUSIONS Rupatadine appeared to be safe and well tolerated and showed a trend towards a reducing proportion of patients with acute dengue who developed DHF. It usefulness when used in combination with other treatment modalities should be explored. TRIAL REGISTRATION International Clinical Trials Registration Platform: SLCTR/2017/024.
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Efficacy of Gamma Globulin Combined with Azithromycin Sequential Therapy in the Treatment of RMPP and Its Effect on Th1/Th2 Cytokine Levels
Qi, J., Jia, F., Tian, H., Yang, S.
Computational and Mathematical Methods in Medicine. 2022;2022:5162768
Abstract
OBJECTIVE To investigate the efficacy of gamma globulin combined with azithromycin sequential therapy in the treatment of children with refractory mycoplasma pneumonia and its effect on Th1/Th2 cytokine levels. METHOD From January 2021 to January 2022, 100 children diagnosed with refractory mycoplasma pneumonia were randomly divided into 2 groups (50 cases in each one), the control group was treated with azithromycin plus comprehensive basic treatment, and the treatment group was treated with combined treatment on the basis of the control group, gamma globulin therapy; the treatment effect and cytokine levels of the two groups were compared. RESULTS Th1, Th2, and Th1/Th2 before treatment were not significantly different between the two groups. Th1, Th2, and Th1/Th2 in the treatment group were significantly downregulated compared with those in the control group after treatment. The levels of IgG, IgA, and IgM in the treatment group were not significantly different from those in the control group before treatment but were significantly upregulated after treatment. IL-10, IL-6, and IL-2 levels were also significantly increased in the treatment group. The disappearance time of clinical symptoms such as fever, cough, and pulmonary rales in the treatment group was significantly shorter than that in the control group, and the cure rate in the treatment group was significantly better than that in the control group. CONCLUSION The clinical effect of gamma globulin combined with azithromycin sequential therapy in the treatment of children with refractory mycoplasma pneumonia is remarkable, which can reduce inflammatory factors, improve patients' immunity, and promote disease recovery.
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8.
Erythropoietin in children with hemolytic uremic syndrome: a pilot randomized controlled trial
Balestracci A, Capone MA, Meni Battaglia L, Toledo I, Martin SM, Beaudoin L, Balbaryski J, Gómez L
Pediatric nephrology (Berlin, Germany). 2022
Abstract
BACKGROUND The efficacy of recombinant human erythropoietin (rHuEPO) in sparing red blood cell (RBC) transfusions in children with hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) is uncertain. METHODS We conducted a pilot randomized controlled open trial between December 2018 and January 2021. Children were randomized to the intervention (subcutaneous rHuEPO 50 U/kg three times weekly until discharge + RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability) or to the control arm (RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability). Primary outcome was the number of RBC transfusions received during hospitalization. Secondary outcomes were to explore whether baseline EPO levels were adequate to the degree of anemia, to correlate selected acute phase parameters with the number of RBC transfusions, and to assess possible adverse events. RESULTS Twelve patients per arm were included; they were comparable at recruitment and throughout the disease course. Median number of RBC transfusions was similar between groups (1.5, p = 0.76). Most patients had baseline EPO levels adequate to the degree of anemia, which did not correlate with the number of transfusions (r = 0.19, p = 0.44). Conversely, baseline (r = 0.73, p = 0.032) and maximum lactic dehydrogenase levels (r = 0.78, p = 0.003), creatinine peak (r = 0.71, p = 0.03) and dialysis duration (r = 0.7, p = 0.04) correlated significantly with RBC requirements. No side effects were recorded. CONCLUSION In children with STEC-HUS, the administration of rHuEPO did not reduce the number of RBC transfusions. Larger studies addressing higher doses and similar severity of kidney failure at rHuEPO initiation (e.g. at start of dialysis) are warranted. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03776851. A higher resolution version of the Graphical abstract is available as Supplementary information.
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9.
A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection
Hughes BL, Clifton RG, Rouse DJ, Saade GR, Dinsmoor MJ, Reddy UM, Pass R, Allard D, Mallett G, Fette LM, et al
The New England journal of medicine. 2021;385(5):436-444
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Abstract
BACKGROUND Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection. METHODS In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed. RESULTS From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo. CONCLUSIONS Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).
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Characteristics and therapy of enteroviral encephalitis: case report and systematic literature review
Wagner JN, Leibetseder A, Troescher A, Panholzer J, von Oertzen TJ
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2021
Abstract
OBJECTIVES Enterovirus (EV) is a frequent cause of encephalitis. The optimal therapeutic approach remains a matter of debate. We present the case of an immunosuppressed patient with EV encephalitis successfully treated with IVIG and conduct a systematic review on the characteristics of EV encephalitis as well as the safety and efficacy of IVIG-therapy. METHODS We conducted a systematic review assessing PubMed, Cochrane Database, Biosis Previews and the ClinicalTrials.gov website to identify all reports on patients with EV encephalitis as of December 31, 2020. Main outcomes assessed were efficacy and safety of the respective therapeutic approach. RESULTS We included a total of 73 papers: one prospective trial, one retro- and prospective case series, one purely retrospective case series, and 70 case reports. The case reports cover a total of 101 patients. The immunosuppressed were at higher risk of contracting EV encephalitis and experiencing lethal courses. Hypogammaglobulinaemia particularly predisposes for EV disease, even with moderate reduction of serum IgG levels. IVIG therapy in the immunosuppressed may confer a survival advantage. CONCLUSIONS IVIG therapy is rarely associated with severe adverse events and may be considered in immunosuppressed patients with EV encephalitis. Future trials should investigate optimal IVIG dosing and route of application, the benefit of antibody-enriched IVIG preparations and the serum immunoglobulin level that should trigger prophylactic replacement.